We have previously found a very good inverse correlation between species life span and the rate at which cultured fibroblasts activate DMBA to a mutagenic form. We now have evidence that there is also a very good inverse correlation between species life span and both the rate at which cultured fibroblasts bind DMBA to their DNA and metabolize BP to water-soluble products. Although the apparent role of drug metabolism is the detoxification of foreign compounds, polycyclic hydrocarbon metabolism by cultured fibroblasts does not appear to serve a detoxifying function. Cells which readily metabolize polycyclic hydrocarbon carcinogens to water-soluble metabolites are also sensitive to the cytotoxic effects of these compounds, while poorly metabolizing cells are relatively resistant. Our data suggest that the capacity of cultured fibroblasts to metabolize polycyclic hydrocarbon carcinogens is closely related to life span in mammalian species, and raise the possibility that the metabolism of these carcinogens to reactive intermediates may contribute to spontaneous cancer.